Download Trends in the prevalence of chronic kidney

Nephrol Dial Transplant (2010) 25: 2557–2564
doi: 10.1093/ndt/gfq062
Advance Access publication 22 February 2010
Trends in the prevalence of chronic kidney disease and its risk factors
in a general Japanese population: The Hisayama Study
Masaharu Nagata1,2, Toshiharu Ninomiya1,2, Yasufumi Doi1,2, Koji Yonemoto1, Michiaki Kubo1,2,
Jun Hata1,2, Kazuhiko Tsuruya2, Mitsuo Iida2 and Yutaka Kiyohara1
1
Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan and 2Department
of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Correspondence and offprint requests to: Toshiharu Ninomiya; E-mail: [email protected]
Abstract
Background. Chronic kidney disease (CKD) is increasingly recognized as a leading public health issue. However,
there are limited data assessing secular trends in the prevalence of CKD in general Asian communities.
Methods. We performed three repeated cross-sectional
surveys of residents aged ≥40 years in 1974 [2118 subjects (participation rate, 81.2%)], 1988 [2741 subjects
(80.9%)] and 2002 [3297 subjects (77.6%)] in a Japanese
community. We compared the prevalence of CKD [one or
both of proteinuria and estimated glomerular filtration
rate (eGFR) < 60 mL/min/1.73 m2] and potential risk factors among the three surveys.
Results. The prevalence of CKD increased significantly
with time in men (13.8% [95% confidence interval
(95% CI), 11.4–16.2%] in 1974, 15.9% [95% CI, 13.6–
18.2%] in 1988 and 22.1% [95% CI, 19.6–24.6%] in
2002; P for trend < 0.001), but not in women (14.3%
[95% CI, 12.2–16.4%], 12.6% [95% CI, 10.9–14.3%]
and 15.3% [95% CI, 13.4–17.2%]; P for trend = 0.97).
The frequencies of individuals with CKD Stages 3–5
(eGFR < 60 mL/min/1.73 m2) increased over the three
decades in both sexes. Despite the widespread use of antihypertensive agents, the proportions of individuals with
CKD who reached blood pressure of <130/80 mmHg were
only 27.0% in men and 47.5% in women. The frequency
of metabolic disorders including diabetes, hypercholesterolaemia and obesity increased over the three decades in
both sexes.
Conclusions. The prevalence of CKD increased significantly in men, but not in women over the last three decades
in a general Japanese population. Our findings support the
requirement for a comprehensive treatment for hypertension and metabolic disorders to reduce the burden of CKD.
Keywords: chronic kidney disease; general population; hypertension;
metabolic disorder; prevalence
proteinuria [1,2], is increasingly recognized as a leading
public health issue. The number of patients with endstage kidney disease has been expanding rapidly and
is predicted to exceed 2 million worldwide by the year
2010 [3]. Furthermore, it has been established that
CKD is a risk factor not only for progressive kidney
failure, but also for cardiovascular morbidity and mortality [4–6].
Several cross-sectional studies have demonstrated that
CKD affects 10–15% of the adult population in developed
Western countries [7–9]. Recent epidemiological studies
have suggested that CKD may be more prevalent in Asian
countries than in developed Western countries [10,11].
Furthermore, it has been reported that the number of patients undergoing dialysis in Asian countries such as Malaysia and Japan has been increasing [12,13]. It is likely
that the prevalence of CKD would increase over time as a
consequence of the accumulation of risk factors such as
hypertension, glucose intolerance, obesity and hypercholesterolaemia, probably owing to the westernization of
the lifestyle in these Asian countries. However, there are
limited data assessing secular trends in the prevalence of
CKD in general Asian communities to date. A better understanding of the past and current prevalence of CKD
and its potential risk factors may provide useful information for the development of management strategies for
CKD.
The Hisayama Study is a community-based cohort study
that has been underway since 1961, with a goal of
estimating the effects of the remarkable lifestyle
changes on the burden of cardiovascular diseases in Japan
[14–17]. The aim of the present study is to assess trends
in the prevalence of CKD and its risk factors over the last
three decades and to examine their relationships.
Subjects and methods
Study population
Introduction
Chronic kidney disease (CKD), most commonly defined
by a reduction in kidney function or the presence of
The town of Hisayama is a suburban community adjacent to Fukuoka
City, a metropolitan area on Kyushu Island in southern Japan. The population of the town has been stable for 50 years and was approximately
8000 in 2008. The age and occupational distributions of the Hisayama
population are almost identical to those of Japan as a whole. Full commu-
© The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
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2558
M. Nagata et al.
nity surveys of the residents have been repeated from the initiation of the
study to date. The study design and characteristics of the subject population have been described in detail elsewhere [14–18]. Briefly, four study
cohorts composed of Hisayama residents aged ≥40 years were established
in 1961, 1974, 1988 and 2002. For this study, we used data from the
cross-sectional surveys conducted at baseline in the latter three cohorts,
which included available data on serum creatinine and proteinuria. The
full community surveys were conducted as follows. In 1974, we invited
all 2629 residents in that age group in the town registry to participate in
the survey by the assistance of the town office, and of those, 2135 (participation rate, 81.2%) consented to participate in the health examination.
After excluding 17 subjects for whom blood samples were unavailable,
2118 subjects (911 men, 1207 women) were enrolled in this study. In
the same manner, 2741 subjects from 2742 participants (participation rate,
80.9%) in 1988 and 3297 subjects from 3298 participants (participation
rate, 77.6%) in 2002 were enrolled in the study. A total of 3059 (38%)
subjects participated in two or more of the three surveys.
glucose tolerance test in 1988 and 2002. Diabetes was regarded as treated
when the subject was under therapy with insulin or hypoglycaemic agents
in 1988 and 2002, but the designation of treated or untreated diabetes was
not made in 1974 due to an absence of information on treatment status.
Serum total cholesterol levels were determined by the Zurkowski method
in 1974 and by the enzymatic method in 1988 and 2002. Hypercholesterolaemia was defined as serum total cholesterol ≥220 mg/dl (5.7 mmol/L)
or current use of a lipid-modifying agent. Treated hypercholesterolaemia
was defined as current use of lipid-modifying agents only in 2002 because information on anti-lipidaemic agents was not available in 1974
and 1988. Body height and weight were measured in light clothing without shoes, and the body mass index (in kilogrammes per square metre)
was calculated. Obesity was defined as a body mass index ≥25 kg/m2.
Metabolic syndrome was defined by using criteria recommended in a joint
interim statement of five major scientific organizations [21]. Information
on medical history, medical treatment, alcohol intake and smoking habits
was obtained through a standard questionnaire by trained interviewers.
Alcohol intake and smoking habits were classified as either current
habitual use or not.
Definition of CKD
Details of the measurement of risk factors in each survey were described
previously [15,16,18,19]. Freshly voided urine samples were tested by the
dipstick method in all surveys. Proteinuria was defined as 1+ or more.
Serum creatinine was measured by the non-compensated Jaffé method
in 1974 and 1988 and the enzymatic method in 2002. Serum samples
were assayed using a Technicon autoanalyser (Technicon Instruments,
Tarrytown, NY) in 1974, a TBA-80S autoanalyser (Toshiba Inc., Tokyo,
Japan) in 1988 and an AU-800 autoanalyser (Olympus Corporation, Tokyo,
Japan) in 2002. The difference between the serum creatinine levels by the
Jaffé method and those by the enzymatic method was calibrated by using 98
serum samples standardized by CRC Corporation (Fukuoka, Japan). The
range of creatinine levels in the samples was 0.5 to 15.2 mg/dl by the Jaffé
method. The conversion equation was estimated by using a simple linear
regression model. The correlation coefficient of this equation was 0.996.
The Jaffé method value was converted to an enzymatic method value by
using the following equation:
Serum creatinine ðenzymatic method ½mg=dlÞ
= 0:9754 serum creatinineðJaff amethod½mg=dlÞ–0:2802:
The estimated glomerular filtration rate (eGFR) was calculated using
the isotope dilution mass spectrometry–traceable creatinine-based fourvariable Modification of Diet in Renal Disease (MDRD) Study equation
with the Japanese Society of Nephrology Chronic Kidney Disease Initiatives coefficient of 0.741 [20]. eGFR was derived using the following
equation:
eGFR mL=min=1:73 m2 = 0:741 175
serum creatinineðenzymatic method½mg=dlÞ−1:154
ageðyearsÞ−0:203
0:742ðif femaleÞ
CKD was defined as either the presence of proteinuria or eGFR < 60
mL/min/1.73 m2. The clinical stages of CKD were classified according to
the recommendations of the National Kidney Foundation Kidney Disease
Outcomes Quality Initiative guidelines [1]: Stage 1 or 2 (eGFR ≥ 60 mL/
min/1.73 m2 and the presence of proteinuria), Stage 3 (eGFR 30–59 mL/
min/1.73 m2) and Stage 4 or 5 (eGFR < 30 mL/min/1.73 m2).
Risk factors
In each survey, blood pressures were measured three times in a sitting
position after at least 5 min of rest, and the mean of the three measurements was used for the analysis. Hypertension was defined as a mean
systolic blood pressure ≥140 mmHg or a mean diastolic blood pressure
≥90 mmHg or a current use of antihypertensive agents. Subjects with hypertension were classified as treated or untreated based on whether or not
they were currently using antihypertensive agents. Diabetes was defined
by fasting glucose concentrations ≥126 mg/dl (7.0 mmol/L) or postprandial glucose concentrations ≥200 mg/dl (11.1 mmol/L) in addition to
medical history of diabetes in 1974 and by those methods and a 75-g oral
Statistical analysis
The prevalences of CKD and each risk factor were adjusted for the age
distribution of the world standard population in 1998 by using the direct
method. The age-adjusted mean values of risk factors were calculated using the analysis of covariance method with age included as a continuous
variable. Trends in the prevalence or mean values of each factor across
survey years were assessed by fitting the logistic or linear regression model with evenly spaced numeric codes for the survey year, respectively. The
age-adjusted relative risk (RR) and its 95% confidence interval (95% CI)
for CKD were estimated by using Poisson regression analysis [22]. The
SAS software package, release 9.2 (SAS Institute, Cary, NC), was used to
perform all statistical analyses. A two-tailed value of P < 0.05 was considered statistically significant.
Results
We compared the age-adjusted prevalence and mean values
of risk factors among the three surveys by sex, as shown in
Table 1. The prevalence of hypertension was constant in
men, but decreased in women from 1974 to 2002. The
prevalence of treated hypertension increased over time,
whereas the prevalence of untreated hypertension decreased in both sexes. Consequently, mean blood pressure
levels decreased over the last three decades. The frequencies of diabetes, hypercholesterolaemia, obesity, metabolic
syndrome and alcohol intake increased with time, whereas
the frequency of smoking habits decreased in both sexes.
The prevalence of diabetes, especially untreated diabetes,
increased with time in both sexes.
Figure 1 presents the age-adjusted prevalence of CKD in
the three surveys by sex. The age-adjusted prevalence of
CKD increased significantly with time in men (13.8%
in 1974, 15.9% in 1988 and 22.1% in 2002; P for trend <
0.001), but not in women (14.3%, 12.6% and 15.3%, respectively; P for trend = 0.9). The prevalence of CKD Stages
3–5 increased 3-fold over time in men (4.8%, 9.4% and
15.7%; P for trend < 0.001) and doubled in women
(5.8%, 9.9% and 11.7%; P for trend < 0.001). Conversely,
the prevalence of CKD Stages 1–2 decreased to two-thirds
in men (9.0%, 6.5% and 6.4%; P for trend = 0.02) and by
half in women (8.5%, 2.7% and 3.4%; P for trend <
0.001). Similar trends in the prevalence of CKD across
the three surveys were also observed in middle-aged
and elderly populations in either sex (Figure 2). There
was a comparable relationship for the prevalence of
24.4 (21.4–27.4)
8.1 (6.4–9.8)
50.6 (46.4–54.8)
61.9 (57.2–66.6)
11.3 (9.1–13.5)
–
72.2 (66.6–77.8)
63.6 (58.4–68.8)
12.4 (10.1–14.7)
–
59 ± 12
136 ± 21
81 ± 12
44.4 (40.6–48.2)
13.8 (11.7–15.9)
30.6 (27.4–33.8)
14.3 (12.1–16.5)
2.7 (1.8–3.6)
11.5 (9.5–13.5)
27.1 (24.0–30.2)
–
56 ± 11
139 ± 21
79 ± 12
42.0 (39.0–46.0)
9.2 (7.2–11.2)
32.8 (29.1–36.5)
2.5 (1.5–3.5)
–
61 ± 12
134 ± 21
81 ± 12
42.5 (39.0–46.0)
19.4 (17.2–21.6)
23.1 (20.4–25.8)
20.6 (18.2–23.0)
5.6 (4.4–6.8)
14.9 (12.8–17.0)
26.9 (23.9–29.9)
6.3 (5.0–7.6)
20.6 (17.9–23.3)
29.4 (26.2–32.6)
13.4 (11.3–15.5)
46.7 (42.6–50.8)
71.2 (66.2–76.2)
<0.001
<0.01
<0.01
0.90
<0.001
<0.001
<0.001
<0.001
0.002
<0.001
–
–
<0.001
<0.001
<0.001
<0.001
21.3 (18.6–24.0)
–
10.2 (8.4–12.0)
5.4 (4.1–6.7)
20.3 (17.8–22.8)
–
57 ± 12
141 ± 21
78 ± 12
42.0 (38.4–45.6)
7.9 (6.4–9.4)
34.1 (30.9–37.3)
2.0 (1.2–2.8)
–
23.9 (21.4–26.4)
16.5 (14.5–18.5)
6.9 (5.5–8.3)
9.8 (8.1–11.5)
60 ± 12
134 ± 21
76 ± 12
34.7 (31.9–37.5)
13.3 (11.6–15.0)
21.3 (19.0–23.6)
9.0 (7.6–10.4)
2.6 (1.8–3.4)
6.4 (5.2–7.6)
41.4 (38.2–44.6)
–
1988
n = 1576
62 ± 13
129 ± 21
76 ± 12
31.3 (28.9–33.7)
16.8 (15.1–18.5)
14.5 (12.7–16.3)
11.5 (10.0–13.0)
2.8 (2.1–3.5)
8.7 (7.3–10.1)
41.0 (38.0–44.0)
8.9 (7.7–10.1)
32.1 (29.3–34.9)
23.8 (21.4–26.2)
18.6 (16.7–20.5)
8.6 (7.0–10.2)
29.5 (26.6–32.4)
2002
n = 1883
<0.001
<0.01
<0.01
<0.001
<0.001
<0.001
<0.001
0.23
0.01
<0.001
–
–
0.004
<0.01
0.002
<0.001
P for trend
Age is not age-adjusted. Values are means ± standard deviations or frequencies. Hypertension was defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg or current use of
antihypertensive agents. Diabetes mellitus was defined by fasting glucose concentrations ≥126 mg/dl (7.0 mmol/L) or postprandial glucose concentrations ≥200 mg/dl (11.1 mmol/L) in 1974 and by a 75-g
oral glucose tolerance test in 1988 and 2002 in addition to a medical history of diabetes according to the recommendations of the American Diabetes Association. Hypercholesterolaemia was defined as serum total
cholesterol ≥220 mg/dl (5.7 mmol/L) or current use of a lipid-modifying agent. Obesity was defined as body mass index ≥25 kg/m2. Treated or untreated statuses were defined as the presence or absence of use of
any medication for the treatment. Metabolic syndrome was defined by using criteria recommended in a joint interim statement of five major scientific organizations.
Age, years
Systolic blood pressure, mmHg
Diastolic blood pressure, mmHg
Hypertension, %
Treated, %
Untreated, %
Diabetes mellitus, %
Treated, %
Untreated, %
Hypercholesterolaemia, %
Treated, %
Untreated, %
Obesity, %
Metabolic syndrome, %
Smoking habits, %
Alcohol intake, %
P for trend
1974
n = 1207
2002
n = 1414
1974
n = 911
1988
n = 1165
Women
Men
Table 1. Age-adjusted prevalence and mean values of risk factors in 1974, 1988 and 2002 by sex
Prevalence of CKD in Japan
2559
2560
M. Nagata et al.
Men
30
*
22.1
CKD
Prevalence, %
25
25
CKD stages 3-5
20
Women
30
*
15.7
15.9
20
15.3
14.3
13.8
15
9.9
9.4
10
10
5.8
4.8
5
5
0
0
1974
1988
2002
1974
1988
Survey year
*P
*
11.7
12.6
15
2002
Survey year
for trend < 0.01
Fig. 1. Trends in the age-adjusted prevalence of CKD in 1974, 1988 and 2002 by sex.
A) <65 years
Men
Women
40
40
30
30
Prevalence, %
CKD
***
20.3
20
***
14.3
13.0
CKD stages 3-5
20
10.4
9.6
10
10
6.1
1974
1988
0
2002
1974
Survey year
B) ≥65 years
Prevalence, %
30
20
40
***
25.7
27.1
21.9
28.5
20
13.0
15.7
10
1974
1988
2002
0
Survey year
*P
28.2 **
23.4
24.6
30
20.4
10
0
2002
Women
*
33.6
40
1988
Survey year
Men
27.7
7.3
12.5 ***
9.2
2.9
2.3
0
9.6
1974
1988
2002
Survey year
for trend < 0.05, **P for trend < 0.01, ***P for trend 0.001
Fig. 2. Trends in the prevalence of CKD by age and sex.
CKD Stages 4–5, but the number of subjects with this
stage of CKD was too small to assess reliably according
to age or sex [eight subjects (0.4%) in 1974, seven subjects (0.3%) in 1988, 33 subjects (1.0%) in 2002 overall].
The number of subjects undergoing dialysis was zero in
1974, one in 1988 and 10 in 2002. The age-adjusted proportion of subjects with proteinuria did not change across
the surveys in men (10.7% in 1974, 7.6% in 1988 and
Prevalence of CKD in Japan
2561
Women
Men
80
BP <140/90 mm Hg
BP <130/80 mm Hg
Frequency, %
60
46.6
47.8
28.2
28.2
27.4
27.4
*
51.1
**
66.6
52.5
47.0
**
**
47.5
47.5
40
27.0
27.0
24.9
24.9
1988
2002
Survey year
1974
30.0
30.0
20
0
*P
1974
1988
Survey year
2002
for trend < 0.05, **P for trend < 0.001
Fig. 3. Age-adjusted frequencies of well-controlled blood pressure in subjects with CKD in 1974, 1988 and 2002 by sex.
Table 2. Age-adjusted prevalence of CKD according to hypertension status in 1974, 1988 and 2002 by sex
Men
Non-hypertension
Prevalence
(95% CI)a, %
RR (95% CI)a
Treated hypertension
Prevalence
(95% CI)a, %
RR (95% CI)a
Untreated hypertension
Prevalence
(95% CI)a, %
RR (95% CI)a
Women
1974
1988
2002
10.9
(7.6–14.2)
1.00
(reference)
11.2
(8.5–13.9)
1.11
(0.76–1.61)
15.5
(12.7–18.3)
1.53
(1.09–2.17)
18.8
(10.7–26.9)
1.00
(reference)
23.8
(16.7–30.9)
1.10
(0.70–1.77)
36.1
(23.7–48.5)
1.16
(0.78–1.81)
16.6
(11.8–21.4)
1.00
(reference)
17.5
(13.0–22.0)
1.00
(0.70–1.43)
28.8
(22.6–35.0)
1.65
(1.19–2.30)
P for trend
0.008
0.48
0.001
1974
1988
2002
11.4
(8.4–14.4)
1.00
(reference)
8.6
(6.6–10.6)
0.79
(0.57–1.11)
12.6
(10.5–14.7)
1.13
(0.84–1.53)
28.8
(15.8–41.8)
1.00
(reference)
19.8
(13.3–26.3)
0.79
(0.54–1.19)
22.5
(10.8–34.2)
0.72
(0.50–1.07)
15.8
(11.9–19.7)
1.00
(reference)
16.7
(11.9–21.5)
0.93
(0.69–1.27)
19.8
(12.5–27.1)
0.93
(0.68–1.28)
P for trend
0.20
0.11
0.66
a
Adjusted for age.
9.6% in 2002; P for trend = 0.65), but decreased significantly with time in women (10.2% in 1974, 3.8% in
1988 and 5.3% in 2002; P for trend < 0.001).
Next, we estimated the frequencies of well-controlled
blood pressure in men and women with CKD in each of
the three surveys (Figure 3). Among subjects with CKD,
the proportion with blood pressure levels of <140/90
mmHg increased from 46.6% in 1974 to 51.1% in
2002 for men and from 47.0% to 66.6% for women,
in parallel with the increment in the proportion of subjects taking antihypertensive agents. The frequency of
blood pressure of <130/80 mmHg was <30% in men
with CKD in all three surveys, whereas it increased
from 24.9% in 1974 to 47.5% in 2002 in women.
Among CKD subjects taking antihypertensive agents in
2002, 36.3% of men and 26.3% of women had a blood
pressure level <140/90 mmHg, and only 11.1% and
12.8%, respectively, had a blood pressure level <130/
80 mmHg. Table 2 shows the age-adjusted prevalence
and RR of CKD by the status of hypertension treatment
among the three surveys by sex. For men, the RR of
presence of CKD increased with time in subjects with
untreated hypertension (P for trend = 0.001), but not
in subjects with treated hypertension (P for trend =
0.48). For women, there was no evidence of significant
differences in the prevalence of CKD over time in any
of the hypertension treatment statuses.
Finally, we assessed the relationship between metabolic
syndrome and the risk of CKD in 1988 and 2002. Metabolic syndrome was associated with an increased risk of prevalent CKD in either sex (Figure 4). The strength of the
relationship did not change over time for men (P for heterogeneity = 0.99), whereas it was attenuated significantly
in 2002 compared with 1988 for women (P for heterogeneity = 0.01).
Discussion
In the present study, we demonstrated that the prevalence
of CKD increased significantly in men, but not in women
from the 1970s to the 2000s in a general Japanese population, whereas CKD Stages 3–5 increased progressively
with time in both sexes. Importantly, more than half of
2562
individuals with CKD did not reach the optimal target levels of blood pressure recommended by the current
guidelines [23,24], despite an increment in the proportion
of subjects taking antihypertensive agents over the last
three decades. Furthermore, our findings implied that
the recent increment in the number of subjects with metabolic disorders is linked to the increasing prevalence of
CKD. These analyses, therefore, would seem to highlight
the importance of the comprehensive management of
metabolic disorders in addition to the strict control of
blood pressure in order to reduce the burden of CKD
in the general Japanese population.
The prevalences of CKD have been reported for several
countries. The National Health and Nutrition Examination
Surveys reported that the age-adjusted prevalence of CKD
Stages 1–4 among subjects aged 20 years or older in the
United States increased from 10.0% in 1988–1994 to
13.1% in 1999–2004 [8]. In Nord-Trondelag, Norway,
the prevalence of CKD Stages 3–5 was 4.4% [9]. CKD
may be more prevalent in Asian countries than in developed Western countries. A cross-sectional study conducted
in 574 024 Japanese subjects over 20 years old demonstrated that the prevalence of CKD Stages 3–5 was 10.6 % in
Japan [11]. Data from the screenings in Okinawa, Japan
showed that the unadjusted prevalence of CKD Stages
3–5 among subjects aged 20 years or older increased between 1993 (10.4%) and 2003 (12.2%) in men, but decreased in women (19.5% in 1993, 17.4% in 2003),
although the average serum creatinine levels increased in
all age categories during this period in either sex [25].
An increasing trend in the prevalence of CKD in men
was thus observed both in our study and Okinawa's study.
The discrepancy observed in women between the two studies may have arisen from a self-selection bias caused by
the low participation rate (<20%) in Okinawa’s study, with
subjects having an underlying disease (e.g. advanced kidney disease) being less likely to participate in the examination. Importantly, the prevalences of CKD in these
studies were estimated on the basis of different eGFR
equations, the direct comparison of which might be inappropriate. A nationwide examination will be needed to estimate the burden of CKD in Japan more reliably.
In the present study, the prevalence of metabolic disorders, such as diabetes, hypercholesterolaemia and obesity,
was found to have increased dramatically over the last
three decades, probably due to the westernization of lifestyle in Japan [26]. In the 2002 survey, diabetes was significantly associated with the likelihood of CKD for both
sexes. Diabetes is an especially serious problem in the prevention strategy for CKD because it has been the leading
cause of end-stage renal disease since 1998 in Japan [13].
Likewise, hypercholesterolaemia and obesity have been
shown to be independent risk factors for CKD [27,28].
Our findings showed a jump in the prevalence of metabolic
disorder from 1974 to 1988 ahead of the increment in the
prevalence in CKD, possibly suggesting a causal association of metabolic disorder with the risk of CKD. In this
study, furthermore, metabolic syndrome, which is defined
as the accumulation of three or more risk factors such as
elevated blood pressure, glucose intolerance, central obesity and dyslipidemia, was associated with an increased
M. Nagata et al.
risk of CKD. Our previous longitudinal study has demonstrated that individuals with metabolic syndrome have
2.1-fold greater risk than those without it [29]. It has also
been reported that clusters of multiple metabolic disorders tended to cause CKD in the several epidemiological
studies [30,31]. Therefore, it is reasonable to suppose that
the increasing prevalence of metabolic disorders has contributed to the increasing trend in CKD, especially CKD
Stages 3–5, in our subjects.
Hypertension is well-established as a powerful risk factor for not only cardiovascular disease, but also CKD [32].
In this study, blood pressure levels significantly declined in
both sexes over the last three decades, probably because of
the widespread use of antihypertensive medication. Nevertheless, about 70% of men with CKD and 50% of women
with CKD did not reach the optimal blood pressure levels
of <130/80 mmHg even in the latest survey. Several clinical trials have demonstrated that blood pressure lowering
was beneficial for the prevention of progressive kidney
disease [33,34] and cardiovascular disease in individuals
with CKD [35–38]. A recent meta-analysis of Japanese cohort studies also revealed that lower blood pressure level is
linearly associated with a lower risk of cardiovascular disease and death in subjects with CKD [39]. These findings,
therefore, suggest that blood pressure should be controlled
more strictly in individuals with CKD, using the recommendations in the current guidelines [23,24].
Our study showed that the prevalence of CKD Stages
1–2 decreased over the last three decades in both sexes.
Importantly, the frequency of women with CKD Stages
1–2 was halved over time, and therefore, the overall
prevalence of CKD did not change. In the 2002 survey,
blood pressure was well-controlled in women, compared
with men (Table 1). It has been established that blood
pressure-lowering therapy, particularly the use of renin–
angiotensin system inhibitors, reduces the risk of the development of proteinuria and subsequent kidney dysfunction
[40–45]. Furthermore, the relationship between metabolic
syndrome and the likelihood of CKD for women tended to
be attenuated from the 1988 survey to the 2002 survey,
possibly due to early interventions, including lifestyle
modification or medications against metabolic disorder.
Thus, our findings imply that optimal management of
blood pressure and metabolic disorder may reduce the
prevalence of CKD in women in the next decade.
Several limitations of our study should be noted. First, it
is well-known that eGFR values calculated using the
MDRD study equation with a single measure of serum creatinine are not fully accurate. In addition, measurement of
serum creatinine was not repeated after an interval of at
least 3 months. Additionally, the values of serum creatinine
were not calibrated using the values from the Cleveland
Clinic, although they were calibrated across the three surveys. These matters may have caused some degree of
misclassification of eGFR levels. Nevertheless, these limitations may have had little effect on our conclusions because the extent of misclassification of eGFR levels
would be similar across the surveys. Second, the method
for measuring serum cholesterol could not be calibrated
across the surveys in this study. However, we believe
that our findings with regard to the trend in the propor-
Prevalence of CKD in Japan
tion of hypercholesterolaemia over time are likely to be
real because the proportion of obesity showed a similar
pattern. Third, a 75-g oral glucose tolerance test was not
performed in 1974. Thus, the prevalence of diabetes in
1974 was likely to be underestimated because the glucose tolerance test is a more sensitive method to diagnose
diabetes. Fourth, the blood pressure levels were estimated
with office blood pressure measurement, but not with
home blood pressure monitoring, likely attenuating the
accuracy of the information about blood pressure control.
Fifth, we were unable to obtain information regarding the
cause of CKD or the type of antihypertensive drugs,
including renin–angiotensin system inhibitors. This information would have enabled a deeper understanding of
our results. Finally, this is a cross-sectional study, and thus,
the data are of limited use in inferring causality between risk
factors and CKD.
Conclusion
In conclusion, the prevalence of CKD increased significantly in men, but not in women from the 1970s to the
2000s in a general Japanese population. Despite the
popularization of antihypertensive medication, blood
pressure was not sufficiently controlled over time to
meet the optimal level recommended by the current
guidelines for patients with CKD. Additionally, the increasing prevalence of metabolic disorders would be expected to play a role in the increasing trend in CKD.
Our findings support the requirement for a comprehensive treatment for hypertension and metabolic disorders
in order to reduce the burden of CKD.
Supplementary data
Supplementary data is available online at http://ndt.
oxfordjournals.org.
Acknowledgements. This study was supported in part by a Grant-in-Aid
for Scientific Research A (No. 18209024) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and a Health
and Labour Sciences Research Grant of the Ministry of Health, Labour
and Welfare (Comprehensive Research on Aging and Health: H20-Chouju-004). The authors thank the residents of the town of Hisayama for their
participation in the survey and the staff of the Division of Health and
Welfare of Hisayama for their cooperation in this study.
Conflicts of interest statement. None declared.
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Received for publication: 23.6.09; Accepted in revised form: 25.1.10
Nephrol Dial Transplant (2010) 25: 2564–2570
doi: 10.1093/ndt/gfq084
Advance Access publication 25 February 2010
Ethnic disparities in prevalence and impact of risk factors of chronic
kidney disease
Charumathi Sabanayagam1,2, Su Chi Lim3, Tien Yin Wong1,2,4, Jeannette Lee5, Anoop Shankar6
and E Shyong Tai7
1
Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge,
Singapore, 2Singapore National Eye Centre and Singapore Eye Research Institute, Singapore, Singapore, 3Department
of Medicine, Alexandra Hospital, Singapore, Singapore, 4Centre for Eye Research Australia, University of Melbourne,
Melbourne, Australia, 5Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National
University of Singapore, Singapore, Singapore, 6Department of Community Medicine, West Virginia University School
of Medicine, Morgantown, WV, USA and 7Department of Medicine, Yong Loo Lin School of Medicine, National University
of Singapore, Singapore, Singapore
Correspondence and offprint requests to: Sabanayagam Charumathi; E-mail: [email protected]
Abstract
Background. There is substantial heterogeneity in literature regarding the epidemiology for chronic kidney disease
(CKD) in different Asian populations. We aimed to assess
the prevalence and risk factors of CKD in a multi-ethnic
Asian population in Singapore.
Methods. We examined 4499 participants of Chinese,
Malay and Indian ethnicity, aged 24–95 years, who
© The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
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